Pretreatment method for enhancing tissue adhesion

ABSTRACT

A closure device is provided for sealing a puncture in a body vessel. The closure device includes an energy delivery device for delivering energy to tissue adjacent the vessel puncture which enhances an adhesiveness of the tissue to a closure composition precursor. The closure device includes a sealer/dilator for dilating tissue adjacent a vessel puncture, at least one closure composition precursor lumen within the sealer/dilator having an entrance port adjacent the proximal end of the sealer/dilator through which one or more fluent closure composition precursors can be delivered into the closure composition precursor lumen and an exit port adjacent the distal end of the sealer/dilator through which the one or more fluent closure composition precursors can be delivered outside the vessel adjacent the vessel puncture, and a plugging catheter for positioning within the vessel puncture, the plugging catheter extending distally from the sealer/dilator and including at least one position sensing mechanism such that the exit port of the closure composition precursor lumen is outside the vessel when the at least one position sensing mechanism is detected to be outside the vessel.

RELATIONSHIP TO COPENDING APPLICATION

[0001] This application is a continuation-in-part of application Ser.No.: 08/963,033, Filed: Nov. 3, 1997, Entitled: Vascular Sealing Device;application Ser. No.: 08/963,082, filed: Nov. 3, 1997, Entitled:In SituFormed Non-fluent Closure Composition; and application Ser. No.:08/963,408, filed: Nov. 3, 1997, entitled: Vascular Sealing Device withMicrowave Antenna which are each continuation-in-parts of ProvisionalU.S. Application Serial No.: 60/033,199; Filed: Dec. 18, 1996, entitled“Universal Introducer”, and a continuation-in-part of U.S. patentapplication Ser. No. 08/731,372 entitled “Thin Layer Ablation Apparatus”by Edwards et al. filed Oct. 11, 1996, which is a continuation-in-partof U.S. patent application Ser. No. 08/319,373 entitled “Thin LayerAblation Apparatus” filed Oct. 6, 1994, which is a continuation-in-partof U.S. application Ser. No. 08/286,862 entitled “Thin Layer AblationApparatus” by Edwards, et al, filed Aug. 4, 1994, which is acontinuation-in-part of U.S. patent application Ser. No. 08/272,162entitled “Thin Layer Ablation Apparatus” by Edwards, et al, filed Jul.7, 1994, which is a continuation-in-part of U.S. patent application Ser.No. 08/265,459 entitled “Thin Layer Ablation Apparatus” by Edwards,filed Jun. 24, 1994, all of which are incorporated by reference.

FIELD OF THE INVENTION

[0002] This invention relates to a vessel closure device, and moreparticularly to a device for effecting the closure of a vessel bydelivering a fluent closure composition precursor and converting thecomposition in situ to a non-fluent closure composition.

BACKGROUND OF THE INVENTION

[0003] A wide variety of surgical procedures are performed by theintroduction of a catheter into a vessel. After the surgical procedureis completed, closure of the vessel at the site where the catheter wasintroduced is needed. Vessel punctures formed in the process ofperforming a catheter based surgical procedure are commonly 1.5 mm to7.0 mm in diameter and can be larger. Closure of these punctures isfrequently complicated by anticoagulation medicine given to the patientwhich interferes with the body's natural clotting abilities.

[0004] Closure of a vessel puncture has traditionally been performed byapplying pressure to the vessel adjacent the puncture site. Thisprocedure requires the continuous attention of at least one medicalstaff member to apply pressure to the vessel puncture site and can takeas long as 30 minutes.

[0005] Devices have been developed for effecting the closure of vesselpunctures through the application of energy. See U.S. Pat. Nos.5,626,601; 5,507,744; 5,415,657; and 5,002,051. Devices have also beendeveloped for effecting the closure of vessel punctures through thedelivery of a mechanical mechanism which mechanically seals thepuncture. See U.S. Pat. Nos.: 5,441,520; 5,441,517; 5,306,254;5,282,827; and 5,222,974. Devices have also been developed for effectingthe closure of vessel punctures through the delivery of a composition toblock the vessel puncture. See U.S. Pat. Nos.5,601,602; 5,591,205;5,441,517; 5,292,332; 5,275,616; 5,192,300; and 5,156,613. Despite thevarious devices that have been developed for closing vessel punctures, aneed still exists for a simple, safe and inexpensive device and methodfor closing vessel punctures.

SUMMARY OF THE INVENTION

[0006] The present invention relates to a device and method for sealinga puncture in a body vessel. In one embodiment, the device has anelongated body having a proximal end and a distal end sized to bepositioned within a lumen of the body vessel; at least one closurecomposition precursor lumen within the elongated body having a entranceport adjacent the proximal end of the elongated body through which oneor more fluent closure composition precursors can be delivered into theclosure composition precursor lumen and an exit port adjacent the distalend of the elongated body through which the one or more fluent closurecomposition precursors can be delivered outside the vessel adjacent thevessel puncture; and at least one position sensing mechanism positioneddistal relative to the exit port such that the exit port is outside thevessel when the at least one position sensing mechanism is detected tobe outside the vessel.

[0007] The closure device of this embodiment may optionally furtherinclude an energy delivery device for delivering energy adjacent thedistal end of the elongated body to the fluent closure compoundprecursor. In one variation, the device includes a microwave antenna fordelivering microwave energy adjacent the distal end of the elongatedbody to the fluent closure compound precursor. In another variation, thedevice includes a waveguide for delivering light energy adjacent thedistal end of the elongated body to the fluent closure compoundprecursor. In yet another variation, the device includes a RF electrodefor delivering RF energy adjacent the distal end of the elongated bodyto the fluent closure compound precursor.

[0008] In another embodiment, the device includes an elongated bodyhaving a proximal end and a distal end sized to be positioned within alumen of the body vessel; at least one closure composition precursorlumen within the elongated body having a entrance port adjacent theproximal end of the elongated body through which one or more fluentclosure composition precursors can be delivered into the closurecomposition precursor lumen and an exit port adjacent the distal end ofthe elongated body through which the one or more fluent closurecomposition precursors can be delivered outside the vessel adjacent thevessel puncture; and a microwave antenna for delivering microwave energyadjacent the distal end of the elongated body to the fluent closurecompound precursor. The microwave antenna according to this embodimentis preferably incorporated onto the elongated body adjacent the bodydistal end.

[0009] In another embodiment, the device includes an elongated bodyhaving a proximal end and a distal end sized to be positioned within alumen of the body vessel; at least one closure composition precursorlumen within the elongated body having a entrance port adjacent theproximal end of the elongated body through which one or more fluentclosure composition precursors can be delivered into the closurecomposition precursor lumen and an exit port adjacent the distal end ofthe elongated body through which the one or more fluent closurecomposition precursors can be delivered outside the vessel adjacent thevessel puncture; a guidewire lumen within the elongated body; and aguidewire including microwave antenna for delivering microwave energyadjacent the distal end of the elongated body to the fluent closurecompound precursor.

[0010] The present invention also relates to a method for sealing apuncture in a body vessel. In one embodiment, the method includes thesteps of delivering a distal end of an elongated body into a lumen ofthe body vessel, the elongated body having at least one closurecomposition precursor lumen with a entrance port adjacent the proximalend of the elongated body through which one or more fluent closurecomposition precursors can be delivered into the closure compositionprecursor lumen and an exit port adjacent the distal end of theelongated body through which the one or more fluent closure compositionprecursors can be delivered outside the vessel adjacent the vesselpuncture, and at least one position sensing mechanism positioned distalrelative to the exit port such that the exit port is outside the vesselwhen the at least one position sensing mechanism is detected to beoutside the vessel; withdrawing the elongated body until the at leastone position sensing mechanism is positioned outside the vessel lumen;delivering one or more fluent closure composition precursors outside thevessel adjacent the vessel puncture; and transforming the one or morefluent closure composition precursors into a non-fluent closurecomposition which seals the vessel puncture.

[0011] In one variation, the method further includes the step ofdelivering energy adjacent the distal end of the elongated body to thefluent closure compound precursor to transform the one or more fluentclosure composition precursors into the non-fluent closure composition.The energy may be microwave energy and the at least one of the one ormore fluent closure composition precursors may optionally include amicrowave energy absorbing material.

[0012] The present invention also relates to a non-fluent closurecomposition for closing a puncture in a vessel. In one embodiment, thenon-fluent closure composition is formed by delivering a fluent closurecomposition precursor to a position outside the vessel adjacent to thepuncture; and transforming the fluent closure composition precursor insitu to a non-fluent closure composition. In another embodiment, thenon-fluent closure composition is formed by delivering two or morefluent closure composition precursors to a position outside the vesseladjacent to the puncture; and mixing the two or more fluent closurecomposition precursors to form a non-fluent closure composition in situadjacent the vessel puncture.

[0013] Transforming the fluent closure composition precursor in situ mayinclude solidifying the closure composition precursor or causing theclosure composition precursor to chemically react with itself to form anon-fluent composition, the chemical reaction optionally being catalyzedby a catalyst or by energy. Energy used in the method may be any form ofenergy including, for example, RF energy and microwave energy. Whenmicrowave energy is used, the closure composition precursor includes amicrowave energy absorbing material.

[0014] The present invention also relates to a method for improving theadhesiveness of tissue surfaces to sealants and adhesives by applyingenergy to a surface of tissue to which a sealant or adhesive is to beapplied. The energy thermally modifies the tissue surface and causes thetissue to be more adherent to sealants and adhesives, such as closurecomposition used in the present invention. The thermal modificationpreferably includes blanching the tissue surface. The thermalmodification is believed to reduce the water content at the tissuesurface, remove materials at the tissue surface which interfere with theadhesiveness of tissue surfaces to sealants and adhesives, change thetopography at the tissue surface, and preferably increase the surfacearea at the tissue surface, all of which serve to increase the tissuesurface's ability to adhere sealants and adhesives. Thermal modificationof the tissue surface may be performed with any suitable form of energy,including for example, electromagnetic energy (RF energy, light, andmicrowave energy), ultrasound, and other thermal heat sources.

[0015] The present invention also relates to a method for improving theadhesiveness of tissue surfaces to sealants and adhesives by applying achemical agent to a surface of tissue to which a sealant or adhesive isto be applied. The chemical agent modifies the tissue surface such thatthe tissue surface is more adherent to sealants and adhesives, such asclosure composition used in the present invention. The chemicalmodification preferably includes denaturing the tissue surface.

[0016] In one variation, basic chemical agents (i.e., having a pHgreater than 7) capable of modifying a tissue surface are used. Examplessuitable basic chemical agents include but are not limited to aqueoussodium bicarbonate, aqueous sodium carbonate, water solutions orsuspensions of alkali or alkali earth oxides and hydroxides, aqueousammonia, water soluble amines such as alkanol amines, basic amino acidssuch as lysine and poly(lysine), aqueous sodium lysinate, and basicproteins such as albumin.

[0017] In another variation, acidic chemical agents (i.e., having a pHless than 7) having an osmolality above that of blood are used which arecapable of modifying a tissue surface.

[0018] In yet another variation, a chemical agent which can serve as atissue etchant is used. Examples of suitable tissue etchants include,but are not limited to salicyclic acid, carboxylic acids, α-hydroxycarboxylic acids, and peroxides.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019]FIG. 1A is a sideview of a closure device according to the presentinvention.

[0020]FIG. 1B is a cross section of the closure device of FIG. 1A.

[0021]FIG. 2 is a cross section of a closure device with a first andsecond closure lumen coupled to first and second closure compositionprecursor sources.

[0022]FIG. 3A is a sideview of a closure device including a guidewirelumen configured to accommodate a guidewire.

[0023]FIG. 3B is a cross section of a closure device illustrated in FIG.3A.

[0024]FIG. 4A illustrates a sheath with a distal end disposed within avessel.

[0025]FIG. 4B illustrates a closure device disposed within the sheathsuch that the distal end of the closure device extends beyond the distalend of the sheath.

[0026]FIG. 4C illustrates the sheath and closure device withdrawn fromthe vessel until the position sensing mechanism is located outside thevessel adjacent the puncture.

[0027]FIG. 4D illustrates a closure composition precursor source coupledto the closure device of FIG. 4C. The closure composition precursor isdelivered through the closure lumen to the puncture.

[0028]FIG. 4E illustrates the puncture after the closure device of FIG.4D is withdrawn from the puncture.

[0029]FIG. 4F illustrates the puncture after the closure device iscompletely withdrawn from the tissue site.

[0030]FIG. 5A is a sideview of a locking mechanism coupled to a closuredevice and threads on a sheath.

[0031]FIG. 5B is a sideview of the locking mechanism of FIG. 5A coupledto the threads on a sheath.

[0032]FIG. 6A illustrates a sheath with a distal end disposed within avessel.

[0033]FIG. 6B illustrates a guidewire disposed within the sheath of FIG.6A.

[0034]FIG. 6C illustrates the sheath of FIG. 6B withdrawn along theguidewire.

[0035]FIG. 6D illustrates a closure device threaded along the guidewireof FIG. 6C until the distal end of the device is disposed within avessel.

[0036]FIG. 6E illustrates the closure device of FIG. 6D after theguidewire has been withdrawn. The closure device is withdrawn until theposition sensing mechanism is located outside the vessel adjacent thepuncture.

[0037]FIG. 6F illustrates a closure composition precursor source coupledto the closure device of FIG. 6E. The closure composition precursor isdelivered through the closure lumen to the puncture.

[0038]FIG. 6G illustrates the puncture after the closure device iscompletely withdrawn from the tissue site.

[0039]FIG. 7A is a sideview of a closure device including a fiber opticring as a energy delivery device.

[0040]FIG. 7B is a cross section of the fiber optic ring of FIG. 7A.

[0041]FIG. 8A is a sideview of a closure device with a contact switch asa position sensing mechanism.

[0042]FIG. 8B is a sideview of a contact switch of FIG. 8A beingcompressed by the vessel wall.

[0043]FIG. 9A illustrates a closure device with a plurality of pressureports coupled to a single position lumen.

[0044]FIG. 9B illustrates a closure device with a plurality of pressureports coupled to the same tubing before the tubing is coupled to thepressure sensor.

[0045]FIG. 9C illustrates a closure device with a plurality of pressureports and first and second closure lumens.

[0046]FIG. 10A is a sideview of a closure device including a balloon asthe position sensing device.

[0047]FIG. 10B illustrates the closure device of FIG. 10A disposedwithin a vessel.

[0048]FIG. 11 illustrates a position sensing mechanism in the form of acurved wire positioned within the vessel lumen.

[0049]FIG. 12A is a cross section of a closure device with a pluralityof closure lumens and a static mixer.

[0050]FIG. 12B is a cross section of a static mixer which is a removablecartridge.

[0051]FIG. 13 is a cross section of a closure device which alternate theprecursor exit ports from a first closure compound with the precursorexit ports of a second closure compound.

[0052]FIG. 14A is a cross section of an anti-backflow valve.

[0053]FIG. 14B is a cross section of an anti-backflow valve.

[0054]FIG. 15A illustrates a flapper valve disposed within the distalend of a closure device.

[0055]FIG. 15B is a sideview of a flapper valve.

[0056]FIG. 16 illustrates an embodiment of a closure device which canthermally pretreat tissue prior to the delivery of a closure compositionin order to enhance the adhesiveness of tissue to the closurecomposition.

[0057]FIG. 17 illustrates a cross section of one possible embodiment ofa closure device according to the present invention which includes anenergy source for pretreating tissue.

[0058]FIG. 18A illustrate a cross section of a first pressure port.

[0059]FIG. 18B illustrates a cross section of a second pressure port.

[0060] FIGS. 19A-19D illustrate a method of using the closure deviceillustrated in FIG. 16.

[0061]FIG. 19A illustrates positioning the plugging catheter within thevessel.

[0062]FIG. 19B illustrates applying pretreatment energy to the vesseland to tissue adjacent the vessel.

[0063]FIG. 19C illustrates positioning the closure device so that theposition sensor is located outside the vessel.

[0064]FIG. 19D illustrates delivering the closure composition precursoradjacent the vessel puncture.

[0065]FIG. 20 illustrates a variation of the embodiment illustrated inFIG. 16 in which the sealer/dilator is a cylindrical, tubular elementhaving a lumen within which the plugging catheter can be moved axially(⇄).

[0066]FIG. 21 illustrates a variation of the embodiment illustrated inFIG. 16 in which the position of the plugging catheter is fixed relativeto the sealer/dilator.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0067]FIGS. 1A and 1B illustrate a closure device 10 according to thepresent invention. The closure device 10 may be used to seal a puncturein a vessel such as a femoral artery.

[0068] The closure device 10 includes an elongated body 12 with aproximal end 14 and a distal end 16 sized to be inserted into a lumen ofa vessel. The surface of the elongated body 12 is preferably made of anon-stick material, such as TEFLON, or coated with a biocompatiblelubricant. Positioned within the elongated body 12 are one or moreclosure lumens which extend from adjacent the proximal end 14 of thedevice to the distal end 16 of the device for introducing a closurecomposition precursor adjacent the vessel puncture site. Illustrated inFIGS. 1A and 1B is a closure device 10 with a single closure lumen 18with a precursor entrance port 20 and at least one precursor exit port22 adjacent the distal end 16. The precursor entrance port 20 ispreferably removably coupleable to a closure composition precursorsource 24 for supplying the closure composition precursor to the closuredevice 10. The closure lumen 18 may optionally contain an anti-backflowvalve 26 to prevent blood from flowing into the closure lumen 18 fromthe vessel.

[0069] The closure composition precursor can be formed of one or morefluent materials that can be flowed from the closure compositionprecursor source 24 to adjacent the device distal end 16 through theclosure lumen 18. The fluent closure composition precursor istransformed into a non-fluent closure composition in situ to effectclosure of the puncture. In a preferred embodiment, energy is applied tothe closure composition precursor to accelerate its transformation intothe non-fluent closure composition. The transformation of the fluentprecursor to a non-fluent closure composition may be the result of aphase change (i.e. solidification) of the precursor or a chemicalmodification of the precursor. For example, the precursor may be formedfrom multiple components which react with each other, optionallyaccelerated by a catalyst or energy. Alternatively, the precursor may beformed from a single component which reacts with itself, also optionallyaccelerated by a catalyst or energy.

[0070] In embodiments where energy is applied, the body 12 includes anenergy delivery device 28 adjacent the distal end 16. The energydelivery device 28 may be designed to deliver one or more differenttypes of energy including but not limited to electromagnetic radiation(RF, microwave, ultraviolet, visible light, laser), ultrasound,resistive heating, exothermic chemical heating, and frictional heating.The energy source may also function to withdraw energy, i.e., performcooling. The closure device 10 may also include an energy sourceattachment mechanism 30 for placing the energy delivery device 28 inenergetic communication with an energy source 32.

[0071] The body 12 further includes at least one position sensingmechanism 34 adjacent the distal end 16 of the closure device 10 forindicating whether the position sensing mechanism 34 is located withinor outside of the vessel 36. The position sensing mechanism 34 should bepositioned on the body 12 distal to the precursor exit port 22 so thatwhen the position sensing mechanism 34 is outside the vessel 36 theprecursor exit port 22 is also outside the vessel 36. FIG. 1Aillustrates the closure device 10 with a single position sensingmechanism 34. As illustrated, the closure device 10 may also include aposition monitor attachment port 38 for coupling the position sensingmechanism 34 to a position monitor 40. Examples of a position sensingmechanisms include, but are not limited to, a pressure port and anelectrical contact switch.

[0072] Other sensors (not shown) may also be positioned on the body 12.For instance, a temperature sensor for measuring temperature adjacentthe distal end 16 of the body 12 and/or an impedance sensor may bepositioned at the distal end 16 of the closure device 10.

[0073] The body 12 can include two or more closure lumens for theintroduction of closure composition precursor. For example, asillustrated in FIG. 2, a second closure lumen 42 may be coupled to asecond closure composition precursor source 44 by a second precursorentrance port 46. The second closure lumen 42 may also contain ananti-backflow valve 26 to prevent blood flow through the second closurelumen 42.

[0074] The closure composition precursor may be introduced adjacent thevessel puncture as a single composition through a single closure lumen.Alternately, a first composition may be introduced through the closurelumen 18 and a second composition can be introduced through the secondclosure lumen 42, as illustrated in FIG. 2. The first and secondcompositions can be the same or different and can be introducedsimultaneously or at different times. The first and second compositionsmay interact to accelerate the transformation to the non-fluent closurecomposition at the tissue site 54, for example, by reacting with eachother or by one catalyzing the solidification of the other..

[0075] FIGS. 3A-3B illustrate another embodiment of the inventionconfigured to be used with a guidewire. As illustrated in FIG. 3A, thebody 12 can include a guidewire lumen 48 configured to accommodate aguidewire. The guidewire lumen 48 can include an anti-backflow valve orhemostasis valve 50. FIG. 3B illustrates a cross-section of the deviceillustrated in FIG. 3B.

[0076] FIGS. 4A-4F illustrate a method of using the closure device 10illustrated in FIGS. 1A-1B. The closure device 10 is used after asurgical procedure where a vessel 36 such as a femoral artery has beenpunctured. Angioplasty is a typical surgery which results in puncturingthe femoral artery with a catheter. After the catheter devices from sucha surgical procedure have been removed, a sheath 52 typically remainswithin a tissue site 54 as illustrated in FIG. 4A. The sheath 52penetrates the skin 56 of the patient and passes through the underlyingtissue to a vessel 60. The distal end 16 of the sheath 52 is positionedthrough a puncture 62 in the vessel 60.

[0077] As illustrated in FIG. 4B, the closure device 10 is inser intothe sheath lumen 64. The position of the closure device 10 within thesheath 52 may be set by fixing the closure device 10 to the sheath. Forexample, as illustrated, the closure device 10 may include a stop collar66 which may engage an upper flange 68 on the sheath 64. The distal end16 of the closure device 10 extends from the sheath 52 such that theposition sensor 30 and precursor exit port 22 are distal relative to thesheath 52 and positioned within the vessel 60.

[0078] As illustrated in FIG. 4C, the sheath 52 and closure device 10are simultaneously withdrawn until the position sensor 30 is sensed tobe located outside the vessel 60. Since the precursor exit port 22 ispositioned distal relative to the position sensor 30, the precursor exitport 22 is necessarily positioned outside the vessel 60 when theposition sensor is outside the vessel 60.

[0079] As illustrated in FIG. 4D, a fluent closure composition precursor70 is delivered through the closure lumen 18 and out the precursor exitport 22 after the precursor exit port 22 is determined to be outside thevessel 60. The fluent closure composition precursor 44 should havesufficiently low viscosity to allow the closure composition precursor toflow through the closure lumen 18. Once delivered, the closurecomposition precursor 44 accumulates adjacent the vessel 60. Thetransformation of the closure composition precursor to a non-fluentclosure composition serves to seal the vessel puncture 62. Energy canoptionally be delivered from the energy delivery device 28 to theclosure composition precursor as illustrated by arrows 72 in order tocause and/or accelerate transformation to the non-fluent closurecomposition. Alternatively or in addition, a catalyst can be added tocatalyze the conversion of the fluent precursor to a non-fluent closurecomposition.

[0080]FIG. 4E illustrates the withdrawal of the closure device 10.

[0081] In FIG. 4F the closure device 10 is completely withdrawn from thetissue site 54 and pressure is being applied at the arrows 74 for asufficient period of time after the closure composition precursor isdelivered to allow the closure composition to transition to non-fluentclosure composition.

[0082] The body 12 can optionally further include a locking mechanism 76for coupling the closure device 10 to the sheath 52. For example, asillustrated in FIGS. 5A and 5B, the locking mechanism 76 can be athreaded nut 78 complementary to threads 80 at the proximal end 14 ofthe sheath 52. When the closure device 10 is positioned within thesheath 52 the threaded nut 78 is turned to engage the threads 80 on thesheath 52 as illustrated in FIG. 5B. As a result, the sheath 52 andclosure device 10 move as a unitary body. Movement as a unitary body isdesirable to prevent the closure device 10 from moving relative to thesheath 52 when the closure device 10 is withdrawn from the tissue site54. Other mechanisms can be used to lock the closure device to a sheathincluding, for example, straps, snap-fit arrangements, bayonet locks,magnets, adhesives, and detents.

[0083] FIGS. 6A-6G illustrate a method of using the closure device 10illustrated in FIGS. 3A-3B which include a guidewire. As discussed withregard to the method illustrated by FIGS. 4A-4F, the method makes use ofa sheath 52 left in place after a surgical procedure. FIG. 6Aillustrates the sheath 52 in place in a tissue site 54 after thesurgical procedure.

[0084] As illustrated in FIG. 6B a guidewire 82 is inserted into thevessel 60 through the sheath lumen 64.

[0085] Pressure is applied to the skin 56 upstream from the puncture 62as shown by arrow 76 in FIG. 6C to prevent bloodflow through the vessel60. The sheath 52 is then withdrawn from the tissue site 54 along theguidewire 82 as illustrated by arrow 84.

[0086] As illustrated in FIG. 6D, the guidewire 82 is then thread withinthe guidewire lumen 48 of the closure device 10 and the distal end 16 ispushed forward through the tissue site 54 until the position sensor 30indicates that the position sensor 30 is within the vessel 60. Thedistal end 16 of the closure device 10 preferably has the same or largerdiameter as the sheath used in the surgical procedure. Since thepuncture 62 has been dilated to the diameter of the sheath 52, thissizing reduces leakage of blood between the puncture 62 and the closuredevice 10.

[0087] As illustrated in FIG. 6E, the closure device 10 is slowlywithdrawn from the vessel 60 until the position sensor 30 indicates thatthe position sensor 30 is located outside the vessel 60. Since theprecursor exit port 22 is positioned proximally relative to the positionsensor 30, withdrawal of the position sensor from the vessel 60 assuresthat the precursor exit port 22 has been withdrawn from the vessel 60.

[0088] As illustrated in FIG. 6F, once the precursor exit port 22 isdetermined to be outside the vessel 60, a closure composition precursor44 is delivered through the closure lumen 18 and out the precursor exitport 22 adjacent the vessel puncture 62.

[0089]FIG. 6G illustrates the complete withdrawal of the closure device10 from the tissue site 54. Pressure is applied at the arrows 86 untildesired transformation of the fluent closure composition precursor tothe non-fluent closure composition is substantially completed.

[0090] The energy delivery device 28 can be optionally used to deliver aform of energy which functions to accelerate the transformation of thefluent closure composition precursor to non-fluent closure composition.Alternatively or in addition, a catalyst can be added to catalyze theconversion of the fluent precursor to a non-fluent closure composition.Most commonly, energy is used to increase the temperature of the closurecomposition precursor. In one embodiment, the energy delivery device 28is a microwave antenna positioned on or within the body 12. Theguidewire 82 can also include a microwave antenna. When microwave energyis employed, the closure composition precursor preferably includesmaterials capable of absorbing microwave energy. Examples of suchmaterials include, but are not limited to, hematite (α-Fe₂O₃), maghemite(y-Fe₂O₃), magnetite (Fe₃O₄), geothite (α-FeOOH), lepidocrocite(y-FeOOH), ferrihydrite, feroxyhyte (δ-FeOOH), akageneite (β-FeOOH)graphite and amorphous carbon.

[0091] The energy delivery device 28 may also be a wave guide 88 fordelivery of UV, visible light or laser energy as illustrated in FIG. 7A.The closure device 10 includes a waveguide collar 90. FIG. 7Billustrates a cross section of the waveguide collar 90. A plurality ofwaveguides 88 are arranged circumferentially around the collar. Thelight is provided to the waveguides 88 through a cable 92 coupled to alight source 94.

[0092] The energy delivery device 28 may also be an electrode fordelivering RF energy. The electrode can be a ring electrode encirclingthe body 12 as illustrated in FIG. 1A or a more localized electrode asillustrated in FIG. 2. The RF supply wires are run through the body 12and coupled to the energy source attachment port 30. Alternatively, RFenergy may be delivered to the closure composition precursor via theguidewire 82. Other types of energy 10 can also be used, including thosethat deliver ultrasound, resistive heating, exothermic chemical heating,other forms of electromagnetic radiation, and frictional heating.

[0093] Referring again to FIG. 1A, one example of a position sensingmechanism 34 is a pressure port coupled to the position monitorattachment port 38 by a position lumen. The position monitor 40 is apressure sensor coupled to the position sensor attachment port bytubing. As a result, an open channel is created between the pressureport and the pressure sensor allowing the pressure sensor to detect thepressure at the port. The pressure within the vessel 60 is elevatedcompared with the pressure in the surrounding tissue. As a result, thesignal from the pressure sensor indicates whether the position port islocated within or outside the vessel 60.

[0094] The position sensing mechanism 34 can also be a contact switch 96as illustrated in FIGS. 8A and 8B. The contact switch is coupled to theposition monitor attachment port 38 by wires run through the body (notshown). When the switch 96 is in contact with the vessel wall the switch96 closes and a circuit (not shown) is completed, however, when theswitch 96 is not in contact with the vessel wall, the switch 96 remainsopen and the circuit is not completed. The circuit is monitored todetermine the position of the closure device 10 relative to the vessel60. Alternatively, the circuit can be coupled to the energy deliverydevice 24 such that the energy cannot be delivered unless the circuit iscompleted. In one embodiment, the device includes a mechanism whichprevents the closure composition from being delivered if the positionsensor is sensed to be within the vessel. As a result, energy will notbe delivered unless the closure device 10 is properly positioned withinthe tissue site 54.

[0095] In a preferred embodiment, the closure device 10 includes two ormore position sensors positioned around the closure device 10 where areading that the sensor is outside the vessel occurs when all of thesensors are outside of the vessel. By having more than one positionsensor around the closure device 10, false readings from one of theposition sensors are reduced or avoided. For instance, if a singleposition sensing mechanism 34 is used, the sensing mechanism may becomepressed against the vessel wall resulting in a pressure drop at theposition sensing mechanism 34. The position monitor 40 would falselyprovide a signal indicating that the position sensing mechanism 34 isoutside the vessel 60. When a second position sensing mechanism isincluded, the second position sensing mechanism would still be exposedto the pressure within the vessel 60. As a result, the position monitor40 would not provide a false signal. FIGS. 9A and 9B illustrate aclosure device 10 with two position sensing mechanisms. In FIG. 9A, twopressure ports are coupled to a single position lumen. In FIG. 9B, eachpressure port is coupled to a separate position lumen but both positionlumens are coupled to the same tubing before the tubing is coupled tothe pressure sensor.

[0096] When the position sensing mechanism 34 is a contact switch or apressure port, the position sensing mechanism 34 is preferablypositioned at least 25 mm from the distal end 16. This positioningassures that the distal end 16 of the closure device 10 remains withinthe vessel 60 when the closure device is positioned to deliver theclosure composition precursor. This feature reduces the risk ofdelivering the closure composition precursor to an improper location onthe vessel or within the vessel.

[0097]FIG. 9C illustrates another embodiment of the closure device 10according to the present invention. The closure device 10 includes aplurality of pressure ports 34 and a first precursor entrance port 20and a second precursor entrance port 46. An energy delivery port 30 iscoupled to a plurality of energy delivery devices 28. The closure device10 includes a guidewire lumen 48 for use with the method described inFIG. 6A-6G.

[0098]FIGS. 10A and 10B illustrate another position sensing mechanism34. A balloon 98 is coupled to the distal end 16 of the closure device10 by a first and second retaining collar 99. The balloon is positionedover an inflation port 100. The balloon is coupled to an inflation bulb102 by an inflation lumen 104 and an inflation tube 106. The balloon 98is deflated when the closure device 10 is positioned within the vessel60. Once the balloon 98 enters the vessel 60, the balloon 98 is inflatedto a diameter greater than the diameter of the sheath 52 and thus thepuncture 62. The closure device 10 is then withdrawn until theresistance of the balloon against the puncture 62 is felt as illustratedin FIG. 10B. The resistance indicates that the precursor exit port 22 isoutside the vessel 60 and properly positioned for application of theclosure composition precursor.

[0099]FIG. 11 illustrates yet another embodiment of a position sensingmechanism 34. According to this embodiment, a curved wire 89 ispositioned within the vessel. As the closure device 10 is withdrawn,resistance is felt when the curved wire 89 is pushed up against theinterior of the vessel lumen. The closure precomposition ports arepositioned such that when the resistance is felt, the precompositionports are known to be positioned outside of the vessel.

[0100] Each position sensing mechanism 34 can be distally positioned0.5-30 mm from the precursor exit port 22 and more preferably 3.0-9.0 mmfrom the precursor exit port 22. These distances allow the closurecomposition precursor to be reliably delivered outside the vessel 60once the closure device 10 is positioned for delivery of the closurecomposition precursor.

[0101] A variety of additional sensors may be used in combination withthe present invention. For example, temperature sensors may bepositioned adjacent the distal end 16 of the closure device 10 fordetecting the temperature adjacent the distal end 16. The temperaturesensors may be a thermocouple positioned on the surface of the body 12(not shown) and hardwired to electrical contacts within a sensor monitorattachment port (not shown). These sensors are useful for regulating theamount of energy being delivered to the vessel 60 and tissue adjacentthe closure device 10 and for preventing tissue damage and ablation dueto excess heat application.

[0102] Impedance sensors may also be employed when RF is used in orderto monitor the amount of energy being delivered to the tissue.

[0103] When the closure composition precursor is formed of two or morecomponents, the closure device 10 can optionally include a static mixer108 for mixing different closure composition precursor components beforethe closure composition precursors exit the precursor exit port or ports22. FIG. 12A illustrates a static mixer 108 incorporated into theclosure device 10. The first closure lumen 18 and the second closurelumen 42 intersect at least one time before terminating in at least oneprecursor exit port 22. The static mixer can also be a cartridge 110incorporated into the body 12 of the closure device 10 as illustrated inFIG. 12B. The intersection of the first and second lumens assures thatthe first and second closure composition precursors are mixed beforereaching the at least one precursor exit port 22.

[0104] The configuration of precursor exit ports can also serve toassure adequate mixing of the first and second closure compositionprecursors. As illustrated in FIG. 13, the precursor exit ports 22corresponding to the first closure composition alternate with theprecursor exit ports corresponding with the second closure composition112. As a result, the first and second closure composition precursorsare mixed outside the closure device 10.

[0105] A backflow valve 26 which is suitable for use in a closure lumenis illustrated in FIGS. 14A and 14B. The valve 26 has a compositionentrance 114 and a composition exit 116. FIG. 14A illustrates that whena fluid flows from the entrance 114 to the exit 116, a diaphragm 118slides forward to allow the closure composition precursor to flow freelythrough the valve 26. FIG. 14B illustrates that when a fluid flows fromthe exit 116 to the entrance 114, the fluid places pressure against thebackside of the diaphragm 118 causing the diaphragm 118 to slide againstthe entrance 114 sealing the entrance 114 and preventing a flow of fluidthrough the valve 26.

[0106] An example of a suitable backflow valve 50 for use in the centrallumen 48 adjacent the distal end of the device is a flapper valve 120 asillustrated in FIGS. 15A and 15B. Examples of backflow valves for thecentral lumen which may be positioned adjacent the proximal end of thedevice include, but are not limited to, duckbill valves, hemostasisvalves, and Tuhoy-Bourse valves. The flapper valve 120 is preferablyformed of an elastomeric material such as medical grade silicone rubber.The configuration, as illustrated by FIG. 15B, may be a cylindricalsection transitioning into a conical portion. The conical portion has aseries of slits 122 which allow various implements to pass through thevalve 50. The thickness of the flaps 124 and the flexibility of theelastomeric material will be balanced to provide memory sufficient toclose the puncture as the implements are withdrawn and provide a fluidseal. Blood pressure against the outer surface of the cone will causethe flapper valve 50 to close more tightly.

[0107] The body 12 is formed of any suitable, relatively flexiblematerial. Suitable materials include, but are not limited to,polyethylene, PEBAX, polytetrafluroethylene (TEFLON) and polyurethane.

[0108] A variety of different closure composition precursors andnon-fluent closure compositions can be used in the present invention.The fluent closure composition precursor and non-fluent closurecomposition should be biocompatible and preferably bioresorbable. Theclosure composition should be also capable of forming a strong punctureseal and be able to seal larger sized vessel punctures, e.g., puncturesformed by 8 french or larger needles. Examples of closure compositionsthat can be used with the device and method of the present include, butare not limited to sealants and adhesives produced by Protein PolymerTechnology; FOCALSEAL produced by Focal; BERIPLAST produced by Centeon(J V Behringwerke & Armour); VIVOSTAT produced by ConvaTec(Bristol-Meyers-Squibb); SEALAGEN produced by Baxter; FIBRX produced byCyoLife; TISSEEL AND TISSUCOL produced by immuno AG; QUIXIL produced byOmrix Biopharm; a PEG-collagen conjugate produced by Cohesion(Collagen); HYSTOACRYL BLUE produced by Davis & Geck; NEXACRYL,NEXABOND, NEXABOND S/C, and TRAUMASEAL produced by Closure Medical(TriPoint Medical); OCTYL CNA produced by Dermabond (Ethicon); TISSUEGLUproduced by Medi-West Pharma; and VETBOND produced by 3M. Examples oftwo part closure compositions which may be used are listed in Table 1.TABLE 1 CLASS OF ADHESIVE PART A PART B (Meth) Acrylic (Meth) acrylicfunctional (Meth) acrylic functional (redox initiated) monomers andmonomers and oligomers with oxidant oligomers with reductant initiatorinitator Polyurethane Poly isocyanate Hydrocarbon polyol, polyetherpolyol, polyester polyol Polyurea Poly isocyanate Hydrocarbon polyamine,polyether polyamine Ionomer Polyvalent metal cation Acrylic acid (co)polymer, alginate Epoxy Epoxy resin Aliphatic polyamine, catalystProtein/dialdehyde Gelatin Glutaraldehyde

[0109] Another aspect of the present invention relates to a method forimproving the adhesiveness of a surface of living tissue by treating thetissue surface with a form of energy which thermally modifies the tissuesurface and renders the surface more readily bonded or adherent totissue adhesives, sealants, glues and the like. The thermal modificationpreferably includes blanching the tissue surface. The thermalmodification is believed to reduce the water content at the tissuesurface, remove materials at the tissue surface which interfere with theadhesiveness of tissue surfaces to sealants and adhesives, change thetopography at the tissue surface, and preferably increase the surfacearea at the tissue surface, all of which serve to increase the tissuesurface's ability to adhere sealants and adhesives.

[0110] In one embodiment, the method includes exposing a tissue surfaceto be so treated, which optionally includes the action of forming newtissue surfaces such as by cutting tissue with a scalpel or tool, or byintroducing a medical instrument into previously continuous tissue suchas with a cannula, introducer, catheter, or trocar, to provide newtissue surface(s) surrounding the instrument. For example, this step isencompassed by the step of introducing a closure device of the presentinvention into tissue.

[0111] After a tissue surface to be treated has been exposed, the tissuesurface is contacted with a source of energy which functions to heat thesurface of the tissue. Examples of suitable forms of energy include butare not limited to electromagnetic energy (RF energy, light, andmicrowave energy), ultrasound, and other thermal heat sources. In oneparticular embodiment, RF energy may be delivered to the tissue surfacefrom a metallic electrode (monopolar) of any convenient shape, such asring or needle. In another particular embodiment, RF energy is deliveredthrough a saline solution provided by a microporous membrane (MPM). Inyet another particular embodiment, the RF energy has an intermittent andvariable waveform, such as so-called “coagulation” waveforms, which canserve to increase the bondability of the tissue surface.

[0112] Energy is applied until a degree of “blanching” has been achievedand the ability to bond to the tissue surface is increased. It isbelieved that the energy thermally modifies the tissue surface andcauses the tissue to be more adherent to sealants and adhesives, such asclosure composition used in the present invention.

[0113] While the pretreatment method is being described herein withregard to its use in combination with a closure device of the presentinvention, it is envisioned that the pretreatment method is a tissuepriming method which may be used to enhance the adhesiveness of anytissue surface to which a tissue glue or sealant is to be applied andthus may be used with other methods for joining tissues other than thosedescribed in this application. It is believed that this method can bebeneficially used in a variety of protocols or procedures which usenon-mechanical agents such as glues, adhesives and sealants to jointissue. It is also believed that this method can be beneficially used inprotocols or procedures which use mechanical mechanisms, such asmechanical fasteners, to join tissue. Further, it is believed that thepretreatment method will be beneficial for improving bonding strength toand between tissue surfaces in procedures relying on chemical adhesion,including covalent bonding, as well as mechanical interlocking.

[0114]FIG. 16 illustrates an embodiment of a closure device 140 whichincludes an energy source for pretreating tissue prior to the deliveryof a closure composition in order to enhance the adhesiveness of tissueto the closure composition. The closure device 140 may be used to seal apuncture in a vessel such as a femoral artery. The closure device 140includes an sealer/dilator 142 with a proximal end 144 and a distal end146 which serves as a sealer and tissue dilator. The surface of thesealer/dilator 142 is preferably made of a non-stick material, such asTEFLON, or coated with a biocompatible lubricant. Positioned within thesealer/dilator 142 are one or more closure lumens which extend fromadjacent the proximal end 144 of the device to the distal end 146 of thedevice for introducing a closure composition precursor adjacent thevessel puncture site. Illustrated in FIG. 16 is a closure device 140with a single closure lumen 148 with a precursor entrance port 150 andat least one precursor exit port 152 adjacent the distal end 146. Theprecursor entrance port 150 is preferably removably coupleable to aclosure composition precursor source 154 for supplying the closurecomposition precursor to the closure device 140. The closure lumen 148may optionally contain an anti-backflow valve 156 to prevent blood fromflowing into the closure lumen 148 from the vessel.

[0115] The closure composition precursor can be formed of one or morefluent materials that can be flowed from the closure compositionprecursor source 154 to adjacent the device distal end 146 through theclosure lumen 148, such as the closure composition precursors describedin this application. The fluent closure composition precursor istransformed into a non-fluent closure composition in situ to effectclosure of the puncture.

[0116] The sealer/dilator includes an energy delivery device 158adjacent the distal end 146 for pretreating the tissue prior todelivering the closure composition precursor to the tissue. The energydelivery device 158 may be designed to deliver one or more differenttypes of energy including but not limited to electromagnetic radiation(RF, microwave, ultraviolet, visible light, laser), ultrasound,resistive heating, exothermic chemical heating, and frictional heating.The closure device 140 also includes an energy source attachmentmechanism 160 for placing the energy delivery device 158 in energeticcommunication with an energy source 162.

[0117] A plugging catheter 163 sized to fit within a vessel lumenextends from the distal end 146 of the sealer/dilator 142. In oneembodiment, the sealer/dilator is actually a cylindrical, tubularelement having a lumen within which the plugging catheter can be movedaxially. The plugging catheter 163 includes at least one positionsensing mechanism 164 for indicating whether the position sensingmechanism 164 is located within or outside of the vessel 166. Theposition sensing mechanism 164 should be positioned on the pluggingcatheter 163 distal to the precursor exit port 152 so that when theposition sensing mechanism 164 is outside the vessel the precursor exitport 152 is also outside the vessel.

[0118]FIG. 16 illustrates the closure device 140 with dual positionsensing mechanisms 164. As illustrated, the closure device 140 may alsoinclude a position monitor attachment port 168 for coupling the positionsensing mechanism 164 to a position monitor 170. Examples of a positionsensing mechanisms include, but are not limited to, a pressure port andan electrical contact switch.

[0119] The sealer/dilator 142 and plugging catheter 163 also include aguidewire lumen configured to accommodate a guidewire 179. The guidewirelumen can include an anti-backflow valve or hemostasis valve.

[0120] Other sensors (not shown) may also be positioned on the pluggingcatheter 163 or the sealer/dilator 142. For instance, a temperaturesensor for measuring temperature adjacent the distal end 146 of thesealer/dilator 142 and/or an impedance sensor may be positioned at thedistal end 146 of the sealer/dilator 140.

[0121] The sealer/dilator 142 can include two or more closure lumens forthe introduction of closure composition precursor. For example, a secondclosure lumen may be coupled to a second closure composition precursorsource by a second precursor entrance port. The second closure lumen mayalso contain an anti-backflow valve to prevent blood flow through thesecond closure lumen.

[0122] The closure composition precursor may be introduced adjacent thevessel puncture as a single composition through a single closure lumen.Alternately, a first composition may be introduced through the closurelumen and a second composition can be introduced through the secondclosure lumen. The first and second compositions can be the same ordifferent and can be introduced simultaneously or at different times.The first and second compositions may interact to accelerate thetransformation to the non-fluent closure composition at the tissue site,for example, by reacting with each other or by one catalyzing thesolidification of the other.

[0123] In a preferred embodiment, the closure device also includes anenergy source for applying energy to the closure composition precursorto accelerate its transformation into the non-fluent closurecomposition. The transformation of the fluent precursor to a non-fluentclosure composition may be the result of a phase change (i.e.solidification) of the precursor or a chemical modification of theprecursor. For example, the precursor may be formed from multiplecomponents which react with each other, optionally accelerated by acatalyst or energy. Alternatively, the precursor may be formed from asingle component which reacts with itself, also optionally acceleratedby a catalyst or energy.

[0124] In embodiments where energy is applied, the energy deliverydevice on the elongated body or an additional energy delivery device isused to deliver one or more different types of energy including but notlimited to electromagnetic radiation (RF, microwave, ultraviolet,visible light, laser), ultrasound, resistive heating, exothermicchemical heating, and frictional heating which serves to accelerate theconversion of the closure composition precursor to a non-fluent closurecomposition.

[0125]FIG. 17 illustrates a cross section of one possible embodiment ofa closure device according to the present invention which includes anenergy source for pretreating tissue. As illustrated, the closure device140 includes an sealer/dilator 142 with a proximal end 144 and a distalend 146 which serves as a sealer and tissue dilator. The surface of thesealer/dilator 142 is preferably made of a non-stick material, such asTEFLON, or coated with a biocompatible lubricant. Positioned within thesealer/dilator 142 is a central lumen 145. The central lumen serves as alumen for a guidewire and plugging catheter. The lumen also serves as alumen for the closure composition precursor. As illustrated, the centrallumen 145 is also connected to a precursor entrance port 150 adjacentthe proximal end 144 of the device and extends to a precursor exit port152 adjacent the distal end 146. The precursor entrance port 150 ispreferably removably coupleable to a closure composition precursorsource (not shown) for supplying the closure composition precursor tothe closure device 140. Tubing 147, such as TYGON tubing, with a valve149 may be attached to the precursor entrance port 150 for facilitatingattachment of a closure composition precursor source (not shown).

[0126] The sealer/dilator includes an energy delivery device 158adjacent the distal end 146 for pretreating the tissue prior todelivering the closure composition precursor to the tissue. The energydelivery device 158 is energetically connected via a conductive metaltube 155 and a wire 151 to an energy source attachment mechanism 160 forplacing the energy delivery device 158 in energetic communication withan energy source (not shown).

[0127] The sealer/dilator also includes threading 177 adjacent itsproximal end for attaching a hemostasis/lock valve 176 to thesealer/dilator distal end.

[0128] A plugging catheter 163 sized to fit within a vessel lumenextends through the central lumen 145 and out the distal end 146 of thesealer/dilator 142. The proximal end of the plugging catheter 163includes a guidewire Luer 157 for positioning a guidewire within aguidewire lumen 169. The plugging catheter 163 can optionally include alocating mark 178 which can be used to indicate how far the pluggingcatheter 163 is extending from the distal end of the sealer/dilator 142.

[0129] The plugging catheter 163 includes first and second positionsensing mechanisms 164A, 164B for indicating whether the first andsecond position sensing mechanisms 164A, 164B are located within oroutside of the vessel. As can be seen, the first position sensingmechanism 164A is distal relative to the second position sensingmechanism 164B. This enables the plugging catheter to be positioned suchthat the first position sensing mechanism 164A is inside the vessel andthe second position sensing mechanism 164B is outside the vessel.

[0130] One example of a position sensing mechanism is a pressure portcoupled to the position monitor attachment port by a position lumen.FIGS. 18A and 18B illustrate a cross section of the plugging catheterwhich includes two position sensing mechanisms. As illustrated in FIG.18A, the first position sensor 164A includes a first position sensorlumen 163A and a pair of first pressure ports 165A. Also illustrated inFIG. 18A is the second position sensor lumen 163B of the second positionsensor 164B. FIG. 18B illustrates a pair of second pressure ports 165Bof the second position sensor 164B.

[0131] As illustrated in FIG. 17, the device also includes marker portcapillary tubes 171A, 171B attached to the first and second positionsensor lumens 163A and 163B respectively.

[0132] As can be seen from FIGS. 18A and 18B, the first and secondpressure ports 165A, 165B are preferably angularly offset relative toeach other so that the sensor ports will not be blocked by a sameobstruction. Similarly, at least a pair of sensor ports is preferablyused in each sensor mechanism so that a given sensor mechanism is notblocked by a single obstruction. These design features enhance thereliability of the sensor mechanisms.

[0133] Also illustrated in FIGS. 18A and 18B is a guidewire lumen 169configured to accommodate a guidewire 179 running through the pluggingcatheter 163. The guidewire lumen can include an anti-backflow valve orhemostasis valve.

[0134] Other sensors may also be positioned on the plugging catheter163. For instance, as illustrated in FIG. 17, a temperature sensor 159for measuring temperature adjacent the distal end 146 of thesealer/dilator 142 may be positioned at the distal end 146 of thesealer/dilator 140. As also illustrated, the temperature sensor 159 isconnected to a temperature sensor wire 173 which can be attached to atemperature sensor connector 175.

[0135] FIGS. 19A-19D illustrate a method of using the closure device 140illustrated in FIG. 16. As illustrated in FIG. 19A, the guidewire 179 isthread within the guidewire lumen of the closure device 140 and theplugging catheter 163 is pushed forward through the tissue site 184until the position sensor 174 indicates that the position sensor 174 iswithin the vessel 166. The plugging catheter 163 of the closure device140 preferably has the same or larger diameter as the sheath used in thesurgical procedure. Since the puncture 181 has been dilated to thediameter of the sheath, this sizing reduces leakage of blood between thepuncture 181 and the closure device 140.

[0136] As illustrated in FIG. 19B, the closure device 140 is pushed intothe tissue until the distal end 146 of the sealer/dilator 142 isadjacent the vessel 166. Because the distal end 146 of thesealer/dilator 142 is significantly larger than the puncture 181 in thevessel 166, resistance will be felt when the distal end 146 of thesealer/dilator 142 is pushed against the vessel 166. Energy 167 is thenapplied by the energy delivery device 158 to pretreat the vessel 166 andtissue adjacent the vessel.

[0137] As illustrated in FIG. 19C, the closure device 140 is then slowlywithdrawn from the vessel 166 until the position sensor 174 indicatesthat the position sensor 174 is located outside the vessel 166. Sincethe precursor exit port 152 is positioned proximally relative to theposition sensor 166, withdrawal of the position sensor 166 from thevessel 174 assures that the precursor exit port 152 has been withdrawnfrom the vessel 166.

[0138] As illustrated in FIG. 19D, once the precursor exit port 152 isdetermined to be outside the vessel 166, a closure composition precursor183 is delivered through the closure lumen 148 and out the precursorexit port 152 adjacent the vessel puncture 181.

[0139]FIG. 20 illustrates a variation of the embodiment illustrated inFIG. 16 in which the sealer/dilator is a cylindrical, tubular elementhaving a lumen within which the plugging catheter can be moved axially(⇄). In this variation, the plugging catheter 163 may include aretraction locking mechanism 190 which limits how far the pluggingcatheter 163 may be withdrawn from the body of the patient through thesealer/dilator. As illustrated, the retraction locking mechanism 190 maybe a member extending from the surface of the plugging catheter 163which prevents the plugging catheter 163 from being withdrawn further.

[0140]FIG. 21 illustrates a variation of the embodiment illustrated inFIG. 16 in which the position of the plugging catheter is fixed relativeto the sealer/dilator. As illustrated, the closure device 140 includesdual position sensing mechanisms 164A, 164B and dual capillaries 171Aand 171B. Preferably, a closure composition is delivered adjacent to thevessel 166 when position sensing mechanism 164A is detected to be withinthe vessel and position sensing mechanism 164B is detected to be outsidethe vessel. The embodiment illustrated further includes a third positionsensing mechanism 164C and capillary 171C which is used as a safetydevice to detect when the sealer/dilator is within the vessel.

[0141] Another aspect of the present invention relates to a method forimproving the adhesiveness of a surface of living tissue by treating thetissue surface with a chemical agent which modifies the tissue surfaceand renders the surface more readily bonded or adherent to tissueadhesives, sealants, glues and the like. The chemical modification mayoptionally include a degree of surface denaturization, a reduction inthe water content at the tissue surface, removal of materials at thetissue surface which interfere with the adhesiveness of tissue surfacesto sealants and adhesives, a change the topography at the tissuesurface, and preferably an increase in the surface area at the tissuesurface, all of which serve to increase the tissue surface's ability toadhere sealants and adhesives.

[0142] In one embodiment, the method includes exposing a tissue surfaceto be so treated, which optionally includes the action of forming newtissue surfaces such as by cutting tissue with a scalpel or tool, or byintroducing a medical instrument into previously continuous tissue suchas with a cannula, introducer, catheter, or trocar, to provide newtissue surface(s) surrounding the instrument. For example, this step isencompassed by the step of introducing a closure device of the presentinvention into tissue.

[0143] After a tissue surface to be treated has been exposed, the tissuesurface is contacted with a suitable chemical agent. In one variation, abasic chemical agent (i.e., having a pH greater than 7) capable ofmodifying a tissue surface is used. Examples suitable basic chemicalagents include but are not limited to aqueous sodium bicarbonate,aqueous sodium carbonate, water solutions or suspensions of alkali oralkali earth oxides and hydroxides, aqueous ammonia, water solubleamines such as alkanol amines, basic amino acids such as lysine andpoly(lysine), aqueous sodium lysinate, and basic proteins such asalbumin. In another variation, an acidic chemical agent (i.e., having apH less than 7) having an osmolality above that of blood is used whichis capable of modifying a tissue surface. In yet another variation, achemical agent which can serve as a tissue etchant is used. Examples ofsuitable tissue etchants include, but are not limited to salicyclicacid, carboxylic acids, α-hydroxy carboxylic acids, and peroxides.

[0144] While the chemical pretreatment method is being described hereinwith regard to its use in combination with a closure device of thepresent invention, it is envisioned that the chemical pretreatmentmethod is a tissue priming method which may be used to enhance theadhesiveness of any tissue surface to which a tissue glue or sealant isto be applied and thus may be used with other methods for joiningtissues other than those described in this application. It is believedthat this method can be beneficially used in a variety of protocols orprocedures which use non-mechanical agents such as glues, adhesives andsealants to join tissue. It is also believed that this method can bebeneficially used in protocols or procedures which use mechanicalmechanisms, such as mechanical fasteners, to join tissue. Further, it isbelieved that the pretreatment method will be beneficial for improvingbonding strength to and between tissue surfaces in procedures relying onchemical adhesion, including covalent bonding, as well as mechanicalinterlocking.

EXAMPLE

[0145] 1. Procedure For Pretreating Tissue

[0146] The following example provides an exemplary procedure forpretreating tissue with energy in order to enhance the adhesiveness ofthe pretreated tissue to an adhesive material.

[0147] Tissue samples were prepared by cutting beef flank steak intospecimens about 35 mm long by 8 mm wide by 2 mm thick with a scalpel.Care was taken to ensure that the muscle fibrils were aligned lengthwiseand the connective tissue between fibrils was intact. A set of 12specimens was soaked in physiologic saline (NaCI; equal to about 0.9%wt.) for 30 minutes just prior to use. The saline soaked tissue was usedas a model for living tissue, which would contain intercellular fluidand blood encountered during any tissue sealing or wound closure medicalprocedure.

[0148] An electrode comprised of a metal cap 6 mm in diameter and 2 mmdeep on the end of a plastic wand was fitted with a thermocouple formeasuring the temperature at the electrode surface. The electrode wasconnected to an Apical, Inc. (Menlo Park, Calif.) Radio Frequency (RF)generator.

[0149] Some of the tissue samples were treated with RF energyimmediately prior to bonding with a tissue adhesive by the followingmethod:

[0150] a) an aluminum pan containing a porous towel saturated with aphysiologic saline solution was electrically connected to the RFgenerator via a standard electrosurgical grounding pad;

[0151] b) a tissue sample to be treated was laid onto the moist toweland the electrode wand touched endwise to one end of the tissue samplesuch that a circular area approximately 6 mm in diameter was in contactwith the electrode and could be treated;

[0152] c) RF energy at a power of 10 watts in the frequency range of300-700 kHz was applied to the electrode and to the tissue surface;

[0153] d) the electrode temperature was monitored during the applicationof energy and increased about 1-2° C./second in the temperature range of25-65° C.;

[0154] e) the electrode treatment temperature was maintained at thedesired level by the Apical RF Generator until treatment was manuallystopped after the desired time at temperature; and

[0155] f) the twelve energy treated tissue samples were set up in pairsto form six lap shear specimens.

[0156] The energy treated tissue samples were then evaluated for theshear strength of the resultant lap bond. A standard gelatin/aldehydetwo part tissue adhesive was spread onto the treated portion of oneenergy treated tissue sample and then compressed against a second energytreated tissue sample to form a lap shear specimen assembly. Bond areawas calculated as the product of the bond width and the overlap of thetissue surfaces.

[0157] Lap shear bond strength evaluation was done on the six replicatespecimen assemblies prepared for each set of control and RF treatmentconditions. Bond strength was measure using a Chatillion Stress-Straininstrument. Bond strengths were taken as the average of the sixreplicates.

[0158] Experimental results from this experiment are tabulated in Table2. As can be seen from the data presented in the table, pre-treatment oftissue with RF energy to a temperature of 50° C. for 5 seconds increasedthe average lap shear bond strength by 34% and increased the greatestobserved strength in the sample population by 66%. These resultsdemonstrate the efficacy of the pre-treatment method for increasing thebond strength of energy treated tissue relative to non- energypretreated tissue.

[0159] While the present invention is disclosed by reference to thepreferred embodiments and examples detailed above, it is to beunderstood that these examples are intended in an illustrative ratherthan limiting sense, as it is contemplated that modifications willreadily occur to those skilled in the art, which modifications will bewithin the spirit of the invention and the scope of the appended claims.TABLE 2 Lap Shear Bond Bond Bond Bond Strength, Sample Width, mmOverlap, mm Failure, X 100 lb g/cm² AVG STD DEV Control 9 10 58 23 NoTreatment 14 8 42 10 Saline Soak 10 10 42 11 9 10 44 22 11 10 48 18 21547 50 C/5 sec 9 10 41 27 Pre-Treatment 8 8 42 28 Saline Soak 7 8 60 46 810 35 19 7 11 68 41 6 10 20 11 290 131

What is claimed is:
 1. A method for sealing a puncture in a body vesselcomprising: delivering a plugging catheter attached to a distal end of asealer/dilator through a vessel puncture into a lumen of a body vessel,the plugging catheter having at least one position sensing mechanism fordetecting when the position sensing mechanism is within the vessel;extending the plugging catheter into the vessel until the sealer/dilatoris positioned adjacent the vessel puncture, the sealer/dilator includinga proximal end, a distal end sized to not enter the vessel, and anenergy delivery device adjacent the distal end for delivering energy totissue adjacent the vessel puncture; delivering energy to tissueadjacent the vessel puncture to enhance an adhesiveness of a surface ofthe tissue to a closure composition precursor; either before or afterdelivering energy, withdrawing the plugging catheter until the positionsensing mechanism is detected to be outside the vessel lumen; deliveringone or more fluent closure composition precursors outside the vesseladjacent the vessel puncture; and transforming the one or more fluentclosure composition precursors into a non-fluent closure compositionwhich seals the vessel puncture.
 2. The method of claim 1 wherein thestep of delivering energy includes delivering a form of energy selectedfrom the group consisting of RF, light, microwave, ultrasound, andthermal energy.
 3. The method of claim 1 wherein the step of deliveringenergy includes delivering a form and amount of energy which blanchesthe tissue surface.
 4. The method of claim 1 wherein the step ofdelivering energy includes delivering a form and amount of energy whichreduces a water content at the tissue surface.
 5. The method of claim 1wherein the step of delivering energy includes delivering a form andamount of energy which reduces an amount of material at the tissuesurface which interferes with the adhesiveness of the tissue surface. 6.The method of claim 1 wherein the step of delivering energy includesdelivering a form and amount of energy which changes a topography of thetissue surface.
 7. The method of claim 1 wherein the step of deliveringenergy includes delivering a form and amount of energy which increases asurface area of tissue at the tissue surface.
 8. A method for enhancingan adhesiveness of a tissue surface comprising: exposing a tissuesurface; delivering energy to the tissue surface which enhances anadhesiveness of the tissue surface; and applying a tissue adhesivematerial to the energy treated tissue surface.
 9. The method of claim 8wherein the step of delivering energy includes delivering a form ofenergy selected from the group consisting of RF, light, microwave,ultrasound, and thermal energy.
 10. The method of claim 8 wherein thestep of delivering energy includes delivering a form and amount ofenergy which blanches the tissue surface.
 11. The method of claim 8wherein the step of delivering energy includes delivering a form andamount of energy which reduces a water content at the tissue surface.12. The method of claim 8 wherein the step of delivering energy includesdelivering a form and amount of energy which reduces an amount ofmaterial at the tissue surface which interferes with the adhesiveness ofthe tissue surface.
 13. The method of claim 8 wherein the step ofdelivering energy includes delivering a form and amount of energy whichchanges a topography of the tissue surface.
 14. The method of claim 8wherein the step of delivering energy includes delivering a form andamount of energy which increases a surface area of tissue at the tissuesurface.
 15. The method of claim 8 wherein the step of exposing a tissuesurface includes cutting tissue so as to create a new tissue surface.16. A method for sealing a puncture in a body vessel comprising:delivering a plugging catheter attached to a distal end of asealer/dilator through a vessel puncture into a lumen of a body vessel,the plugging catheter having at least one position sensing mechanism fordetecting when the position sensing mechanism is within the vessel;extending the plugging catheter into the vessel until the sealer/dilatoris positioned adjacent the vessel puncture, the sealer/dilator includinga proximal end, and a distal end sized to not enter the vessel;delivering a chemical pretreatment agent to tissue adjacent the vesselpuncture to enhance an adhesiveness of a surface of the tissue to aclosure composition precursor; either before or after delivering energy,withdrawing the plugging catheter until the position sensing mechanismis detected to be outside the vessel lumen; delivering one or morefluent closure composition precursors outside the vessel adjacent thevessel puncture; and transforming the one or more fluent closurecomposition precursors into a non-fluent closure composition which sealsthe vessel puncture.
 17. The method of claim 16 wherein the step ofdelivering a chemical pretreatment agent includes delivering a basicchemical agent.
 18. The method of claim 17 wherein the basic chemicalagent is selected from the group consisting of aqueous sodiumbicarbonate, aqueous sodium carbonate, solution of one or more alkali oralkali earth oxides, suspension of one or more alkali or alkali earthoxides, a hydroxide, aqueous ammonia, a water soluble amine, a basicamino acid, aqueous sodium lysinate, and a basic protein.
 19. The methodof claim 16 wherein the step of delivering a chemical pretreatment agentincludes delivering an acidic chemical agent.
 20. The method of claim 19wherein the acidic chemical agent has an osmolality above that of blood.21. The method of claim 16 wherein the step of delivering a chemicalpretreatment agent includes delivering a tissue etchant.
 22. The methodof claim 19 wherein the tissue etchant is selected from the groupconsisting of salicyclic acid, carboxylic acids, α-hydroxy carboxylicacids, and peroxides.
 23. The method of claim 16 wherein the step ofdelivering a chemical pretreatment agent includes delivering a form andamount of a chemical pretreatment agent which reduces a water content atthe tissue surface.
 24. The method of claim 16 wherein the step ofdelivering a chemical pretreatment agent includes delivering a form andamount of a chemical pretreatment agent which interferes with theadhesiveness of the tissue surface.
 25. The method of claim 16 whereinthe step of delivering a chemical pretreatment agent includes deliveringa form and amount of a chemical pretreatment agent which changes atopography of the tissue surface.
 26. The method of claim 16 wherein thestep of delivering a chemical pretreatment agent includes delivering aform and amount of a chemical pretreatment agent which increases asurface area of tissue at the tissue surface.
 27. A method for enhancingan adhesiveness of a tissue surface comprising: exposing a tissuesurface; delivering a chemical agent to the tissue surface whichenhances an adhesiveness of the tissue surface; and applying a tissueadhesive material to the chemically treated tissue surface.
 28. Themethod of claim 27 wherein the step of delivering a chemicalpretreatment agent includes delivering a basic chemical agent.
 29. Themethod of claim 28 wherein the basic chemical agent is selected from thegroup consisting of aqueous sodium bicarbonate, aqueous sodiumcarbonate, solution of one or more alkali or alkali earth oxides,suspension of one or more alkali or alkali earth oxides, a hydroxide,aqueous ammonia, a water soluble amine, a basic amino acid, aqueoussodium lysinate, and a basic protein.
 30. The method of claim 27 whereinthe step of delivering a chemical pretreatment agent includes deliveringan acidic chemical agent.
 31. The method of claim 30 wherein the acidicchemical agent has an osmolality above that of blood.
 32. The method ofclaim 27 wherein the step of delivering a chemical pretreatment agentincludes delivering a tissue etchant.
 33. The method of claim 32 whereinthe tissue etchant is selected from the group consisting of salicyclicacid, carboxylic acids, α-hydroxy carboxylic acids, and peroxides. 34.The method of claim 27 wherein the step of delivering a chemicalpretreatment agent includes delivering a form and amount of a chemicalpretreatment agent which reduces a water content at the tissue surface.35. The method of claim 27 wherein the step of delivering a chemicalpretreatment agent includes delivering a form and amount of a chemicalpretreatment agent which interferes with the adhesiveness of the tissuesurface.
 36. The method of claim 27 wherein the step of delivering achemical pretreatment agent includes delivering a form and amount of achemical pretreatment agent which changes a topography of the tissuesurface.
 37. The method of claim 27 wherein the step of delivering achemical pretreatment agent includes delivering a form and amount of achemical pretreatment agent which increases a surface area of tissue atthe tissue surface.
 38. A closure device for sealing a puncture in abody vessel comprising: a sealer/dilator for dilating tissue adjacent avessel puncture, the sealer/dilator including a proximal end and adistal end sized to not enter the vessel, the sealer dilator includingan energy delivery device adjacent the distal end for delivering energyto tissue adjacent the vessel puncture which enhances an adhesiveness ofthe tissue to a closure composition precursor; at least one closurecomposition precursor lumen within the sealer/dilator having an entranceport adjacent the proximal end of the sealer/dilator through which oneor more fluent closure composition precursors can be delivered into theclosure composition precursor lumen and an exit port adjacent the distalend of the sealer/dilator through which the one or more fluent closurecomposition precursors can be delivered outside the vessel adjacent thevessel puncture; and a plugging catheter for positioning within thevessel puncture, the plugging catheter extending distally from thesealer/dilator and including at least one position sensing mechanismsuch that the exit port of the closure composition precursor lumen isoutside the vessel when the at least one position sensing mechanism isdetected to be outside the vessel.
 39. The closure device of claim 38wherein the at least one position sensing mechanism is a pressure port.40. The closure device of claim 38 wherein the at least one positionsensing mechanism is a contact switch.
 41. The closure device of claim38 wherein the at least one position sensing mechanism is an inflatableballoon positioned adjacent the distal end and mounted over an inflationport.
 42. The closure device of claim 38 wherein, the at least oneposition sensing mechanism is located 0.5-30.0 mm from the precursorexit port.
 43. The closure device of claim 38 wherein, the at least oneposition sensing mechanism is located 3.0-9.0 mm from the precursor exitport.
 44. The closure device of claim 38 wherein, the at least oneposition sensing mechanism is located 25 mm from the distal end.
 45. Theclosure device of claim 38 wherein the energy delivery device delivers aform of energy selected from the group consisting of RF, light,microwave, ultrasound, and thermal energy.
 46. The closure device ofclaim 38 further comprising: a temperature sensor positioned on eitherthe sealer/dilator or plugging catheter for detecting a temperature oftissue during the delivery of energy by the energy delivery device. 47.The closure device of claim 46 wherein, the temperature sensor is athermocouple.
 48. The closure device of claim 38 wherein the deviceincludes at least two closure composition precursor lumens.
 49. Theclosure device of claim 48 wherein each of the at least two closurecomposition precursor lumens has an exit port for separately deliveringa fluent closure composition precursor adjacent the distal end of thesealer/dilator.
 50. The closure device of claim 48 wherein each of theat least two closure composition precursor lumens include at least twoexit ports, the exit ports of the at least two lumens beingalternatively positioned around the distal end of the sealer/dilator.51. The closure device of claim 49 wherein the at least two closurecomposition precursor lumens are connected within the sealer/dilator tocause mixing of closure composition precursor carried within each lumen.52. The closure device of claim 51 wherein the at least two closurecomposition precursor lumens are connected within the sealer/dilator bya static mixer to cause mixing of closure composition precursor carriedwithin each lumen.
 53. The closure device of claim 38 wherein theclosure composition precursor lumen includes at least one backflowvalve.
 54. The closure device of claim 38 further comprising a guidewirelumen.